Widening ethnic inequities in heart failure incidence in New Zealand.

OBJECTIVE: Ethnic inequities in heart failure (HF) have been documented in several countries. This study describes New Zealand (NZ) trends in incident HF hospitalisation by ethnicity between 2006 and 2018. METHODS: Incident HF hospitalisations in ≥20-year-old subjects were identified through International Classification of Diseases, 10th Revision-coded national hospitalisation records. Incidence was calculated for different ethnic, sex and age groups and were age standardised. Trends were estimated with joinpoint regression. RESULTS: Of 116 113 incident HF hospitalisations, 12.8% were Maori, 5.7% Pacific people, 3.0% Asians and 78.6% Europeans/others. 64% of Maori and Pacific patients were aged <70 years, compared with 37% of Asian and 19% of European/others. In 2018, incidence rate ratios compared with European/others were 6.0 (95% CI 4.9 to 7.3), 7.5 (95% CI 6.0 to 9.4) and 0.5 (95% CI 0.3 to 0.8) for Maori, Pacific people and Asians aged 20-49 years; 3.7 (95% CI 3.4 to 4.0), 3.6 (95% CI 3.2 to 4.1) and 0.5 (95% CI 0.4 to 0.6) for Maori, Pacific people and Asians aged 50-69 years; and 1.5 (95% CI 1.4 to 1.6), 1.5 (95% CI 1.3 to 1.7) and 0.5 (95% CI 0.5 to 0.6) for Maori, Pacific people and Asians aged ≥70 years. Between 2006 and 2018, ethnicity-specific rates diverged in ≥70-year-old subjects due to a decline in European/others (annual percentage change (APC) -2.0%, 95% CI -2.5% to -1.6%) and Asians (APC -3.3%, 95% CI -4.4% to -2.1%), but rates remained unchanged for Maori and Pacific people. In contrast, regardless of ethnicity, rates either increased or remained unchanged in <70-year-old subjects. CONCLUSION: Ethnic inequities in incident HF hospitalisation have widened in NZ over the past 13 years. Urgent action is required to address the predisposing factors that lead to development of HF in Maori and Pacific people.

Titration of medications and outcomes in multi-ethnic heart failure cohorts (with reduced ejection fraction) from Singapore and New Zealand.

AIMS: We investigated titration patterns of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs) and beta-blockers, quality of life (QoL) over 6 months, and associated 1 year outcome [all-cause mortality/heart failure (HF) hospitalization] in a real-world population with HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Participants with HFrEF (left ventricular ejection fraction <40%) from a prospective multi-centre study were examined for use and dose [relative to guideline-recommended maintenance dose (GRD)] of ACEis/ARBs and beta-blockers at baseline and 6 months. 'Stay low' was defined as <50% GRD at both time points, 'stay high' as ≥50% GRD, and 'up-titrate' and 'down-titrate' as dose trajectories. Among 1110 patients (mean age 63 ± 13 years, 16% women, 26% New York Heart Association Class III/IV), 714 (64%) were multi-ethnic Asians from Singapore and 396 were from New Zealand (mainly European ethnicity). Baseline use of either ACEis/ARBs or beta-blockers was high (87%). Loop diuretic was prescribed in >80% of patients, mineralocorticoid receptor antagonist in about half of patients, and statins in >90% of patients. At baseline, only 11% and 9% received 100% GRD for each drug class, respectively, with about half (47%) achieving ≥50% GRD for ACEis/ARBs or beta-blockers. At 6 months, a large majority remained in the 'stay low' category, one third remained in 'stay high', whereas 10-16% up-titrated and 4-6% down-titrated. Patients with lower (vs. higher) N-terminal pro-beta-type natriuretic peptide levels were more likely to be up-titrated or be in 'stay high' for ACEis/ARBs and beta-blockers (P = 0.002). Ischaemic aetiology, prior HF hospitalization, and enrolment in Singapore (vs. New Zealand) were independently associated with higher odds of 'staying low' (all P < 0.005) for prescribed doses of ACEis/ARBs and beta-blockers. Adjusted for inverse probability weighting, ≥100% GRD for ACEis/ARBs [hazard ratio (HR) = 0.42; 95% confidence interval (CI) 0.24-0.73] and ≥50% GRD for beta-blockers (HR = 0.58; 95% CI 0.37-0.90) (vs. Nil) were associated with lower hazards for 1 year composite outcome. Country of enrolment did not modify the associations of dose categories with 1 year composite outcome. Higher medication doses were associated with greater improvements in QoL. CONCLUSIONS: Although HF medication use at baseline was high, most patients did not have these medications up-titrated over 6 months. Multiple clinical factors were associated with changes in medication dosages. Further research is urgently needed to investigate the causes of lack of up-titration of HF therapy (and its frequency), which could inform strategies for timely up-titration of HF therapy based on clinical and biochemical parameters.

Identifying Candidate Circulating RNA Markers for Coronary Artery Disease by Deep RNA-Sequencing in Human Plasma.

Advances in RNA sequencing (RNA-Seq) have facilitated transcriptomic analysis of plasma for the discovery of new diagnostic and prognostic markers for disease. We aimed to develop a short-read RNA-Seq protocol to detect mRNAs, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in plasma for the discovery of novel markers for coronary artery disease (CAD) and heart failure (HF). Circulating cell-free RNA from 59 patients with stable CAD (half of whom developed HF within 3 years) and 30 controls was sequenced to a median depth of 108 paired reads per sample. We identified fragments from 3986 messenger RNAs (mRNAs), 164 long non-coding RNAs (lncRNAs), 405 putative novel lncRNAs and 227 circular RNAs in plasma. Circulating levels of 160 mRNAs, 10 lncRNAs and 2 putative novel lncRNAs were altered in patients compared with controls (absolute fold change >1.2, p < 0.01 adjusted for multiple comparisons). The most differentially abundant transcripts were enriched in mRNAs encoded by the mitochondrial genome. We did not detect any differences in the plasma RNA profile between patients who developed HF compared with those who did not. In summary, we show that mRNAs, lncRNAs and circular RNAs can be reliably detected in plasma by deep RNA-Seq. Multiple coding and non-coding transcripts were altered in association with CAD, including several mitochondrial mRNAs, which may indicate underlying myocardial ischaemia and oxidative stress. If validated, circulating levels of these transcripts could potentially be used to help identify asymptomatic individuals with established CAD prior to an acute coronary event.

Contrasting trends in heart failure incidence in younger and older New Zealanders, 2006-2018.

OBJECTIVE: Studies indicate that age-standardised heart failure (HF) incidence has been decreasing internationally; however, contrasting trends in different age groups have been reported, with rates increasing in younger people and decreasing in the elderly. We aimed to describe age-specific trends in HF incidence in New Zealand (NZ). METHODS: In this nationwide data linkage study, we used routinely collected hospitalisation data to identify incident HF hospitalisations in NZ residents aged ≥20 years between 2006 and 2018. Age-specific and age-standardised incidence rates were calculated for each calendar year. Joinpoint regression was used to compare incidence trends. RESULTS: 116 113 incident HF hospitalisations were identified over the 13-year study period. Between 2006 and 2013, age-standardised incidence decreased from 403 to 323 per 100 000 (annual percentage change (APC) -2.6%, 95% CI -3.6 to -1.6%). This reduction then plateaued between 2013 and 2018 (APC 0.8%, 95% CI -0.8 to 2.5%). Between 2006 and 2018, rates in individuals aged 20-49 years old increased by 1.5% per year (95% CI 0.3 to 2.7%) and decreased in those aged ≥80 years old by 1.2% per year (95% CI -1.7 to -0.7%). Rates in individuals aged 50-79 years old initially declined from 2006 to 2013, and then remained stable or increased from 2013 to 2018. The proportion of HF hospitalisations associated with ischaemic heart disease decreased from 35.1% in 2006 to 28.0% in 2018. CONCLUSION: HF remains an important problem in NZ. The decline in overall incidence has plateaued since 2013 due to increasing rates of HF in younger age groups despite an ongoing decline in the elderly.

Temporal trends in the burden of heart failure.

Heart failure is a common healthcare problem associated with high morbidity and mortality. The burden of heart failure is changing; increases secondary to an ageing population may be offset by improved primary cardiovascular prevention and advances in heart failure therapies. In this review, we evaluate recent international trends in heart failure incidence, morbidity and mortality. Although the age-standardised incidence of heart failure has been decreasing since 2000, the incidence in those age groups <55 years is increasing with patients being diagnosed at younger ages. Despite improvements in therapies for heart failure, prognosis still remains poor with up to one-third of patients not surviving beyond 1 year following diagnosis and no improvements in mortality over the past 10 years. The case-mix of heart failure patients is changing with a greater proportion having non-ischaemic aetiology and preserved ejection fraction, and a higher prevalence of non-cardiovascular comorbidity and mortality.

Development and validation of a cardiovascular risk score for patients in the community after acute coronary syndrome.

OBJECTIVE: Following acute coronary syndrome (ACS), patients are managed long-term in the community, yet few tools are available to guide patient-clinician communication about risk management in that setting. We developed a score for predicting cardiovascular disease (CVD) risk among patients managed in the community after ACS. METHODS: Adults aged 30-79 years with prior ACS were identified from a New Zealand primary care CVD risk management database (PREDICT) with linkage to national mortality, hospitalisation, pharmaceutical dispensing and regional laboratory data. A Cox model incorporating clinically relevant factors was developed to estimate the time to a subsequent fatal or non-fatal CVD event and transformed into a 5-year risk score. External validation was performed in patients (Coronary Disease Cohort Study) assessed 4 months post-ACS. RESULTS: The PREDICT-ACS cohort included 13 703 patients with prior hospitalisation for ACS (median 1.9 years prior), 69% men, 58% European, median age 63 years, who experienced 3142 CVD events in the subsequent 5 years. Median estimated 5 year CVD risk was 24% (IQR 17%-35%). The validation cohort consisted of 2014 patients, 72% men, 92% European, median age 67 years, with 712 CVD events in the subsequent 5 years. Median estimated 5-year risk was 33% (IQR 24%-51%). The risk score was well calibrated in the derivation and validation cohorts, and Harrell's c-statistic was 0.69 and 0.68, respectively. CONCLUSIONS: The PREDICT-ACS risk score uses data routinely available in community care to predict the risk of recurrent clinical events. It was derived and validated in real-world contemporary populations and can inform management decisions with patients living in the community after experiencing an ACS.

Convalescent troponin and cardiovascular death following acute coronary syndrome.

OBJECTIVES: High-sensitivity cardiac troponin testing is used in the diagnosis of acute coronary syndromes but its role during convalescence is unknown. We investigated the long-term prognostic significance of serial convalescent high-sensitivity cardiac troponin concentrations following acute coronary syndrome. METHODS: In a prospective multicentre observational cohort study of 2140 patients with acute coronary syndrome, cardiac troponin I concentrations were measured in 1776 patients at 4 and 12 months following the index event. Patients were stratified into three groups according to the troponin concentration at 4 months using the 99th centile (women>16 ng/L, men>34 ng/L) and median concentration of those within the reference range. The primary outcome was cardiovascular death. RESULTS: Troponin concentrations at 4 months were measurable in 99.0% (1759/1776) of patients (67±12 years, 72% male), and were ≤5 ng/L (median) and >99th centile in 44.8% (795) and 9.3% (166), respectively. There were 202 (11.4%) cardiovascular deaths after a median of 4.8 years. After adjusting for the Global Registry of Acute Coronary Events score, troponin remained an independent predictor of cardiovascular death (HR 1.4, 95% CI 1.3 to 1.5 per doubling) with the highest risk observed in those with increasing concentrations at 12 months. Patients with 4-month troponin concentrations >99th centile were at increased risk of cardiovascular death compared with those ≤5 ng/L (29.5% (49/166) vs 4.3% (34/795); adjusted HR 4.9, 95% CI 3.8 to 23.7). CONCLUSIONS: Convalescent cardiac troponin concentrations predict long-term cardiovascular death following acute coronary syndrome. Recognising this risk by monitoring troponin may improve targeting of therapeutic interventions. TRIAL REGISTRATION NUMBER: ACTRN12605000431628;Results.

Patterns of multi-morbidity and prediction of hospitalisation and all-cause mortality in advanced age.

Background: multi-morbidity is associated with poor outcomes and increased healthcare utilisation. We aim to identify multi-morbidity patterns and associations with potentially inappropriate prescribing (PIP), subsequent hospitalisation and mortality in octogenarians. Methods: life and Living in Advanced Age; a Cohort Study in New Zealand (LiLACS NZ) examined health outcomes of 421 Maori (indigenous to New Zealand), aged 80-90 and 516 non-Maori, aged 85 years in 2010. Presence of 14 chronic conditions was ascertained from self-report, general practice and hospitalisation records and physical assessments. Agglomerative hierarchical cluster analysis identified clusters of participants with co-existing conditions. Multivariate regression models examined the associations between clusters and PIP, 48-month hospitalisations and mortality. Results: six clusters were identified for Maori and non-Maori, respectively. The associations between clusters and outcomes differed between Maori and non-Maori. In Maori, those in the complex multi-morbidity cluster had the highest prevalence of inappropriately prescribed medications and in cluster 'diabetes' (20% of sample) had higher risk of hospitalisation and mortality at 48-month follow-up. In non-Maori, those in the 'depression-arthritis' (17% of the sample) cluster had both highest prevalence of inappropriate medications and risk of hospitalisation and mortality. Conclusions: in octogenarians, hospitalisation and mortality are better predicted by profiles of clusters of conditions rather than the presence or absence of a specific condition. Further research is required to determine if the cluster approach can be used to target patients to optimise resource allocation and improve outcomes.

Developing and validating a cardiovascular risk score for patients in the community with prior cardiovascular disease.

OBJECTIVE: Patients with atherosclerotic cardiovascular disease (CVD) vary significantly in their risk of future CVD events; yet few clinical scores are available to aid assessment of risk. We sought to develop a score for use in primary care that estimates short-term CVD risk in these patients. METHODS: Adults aged <80 years with prior CVD were identified from a New Zealand primary care cohort study (PREDICT), and linked to national mortality, hospitalisation and dispensing databases. A Cox model with an outcome of myocardial infarction, stroke or CVD death within 2 years was developed. External validation was performed in a cohort from the UK. RESULTS: 24 927 patients, 63% men, 63% European, median age 65 years (IQR 58-72 years), experienced 1480 CVD events within 2 years after a CVD risk assessment. A risk score including ethnicity, comorbidities, body mass index, creatine creatinine and treatment, in addition to established risk factors used in primary prevention, predicted a median 2-year CVD risk of 5.0% (IQR 3.5%-8.3%). A plot of actual against predicted event rates showed very good calibration throughout the risk range. The score performed well in the UK cohort but overestimated risk for those at highest risk, who were predominantly patients defined as having heart failure. CONCLUSIONS: The PREDICT-CVD secondary prevention score uses routine measurements from clinical practice that enable it to be implemented in a primary care setting. The score will facilitate risk communication between primary care practitioners and patients with prior CVD, particularly as a resource to show the benefit of risk factor modification.

Management and Long-Term Outcome of Acute Coronary Syndrome Patients Presenting with Heart Failure in a Contemporary New Zealand Cohort (ANZACS-QI 4).

BACKGROUND: Acute heart failure (HF) associated with an acute coronary syndrome (ACS) predicts adverse outcome. There have been important recent improvements in ACS management. Our aim was to describe the management and outcomes in those with and without HF in a contemporary ACS cohort. METHODS: Consecutive patients presenting with ACS between 2007 and 2011 were enrolled in the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry. Outcomes and medication dispensing were obtained using anonymised linkage to national data sets. A summary pharmacotherapy measure of "quadruple therapy" was defined as dispensing of at least one agent from each of the four evidence-based classes - anti-platelet, statin, angiotensin converting enzyme inhibitor/angiotensin receptor blocker and beta blocker. RESULTS: Of 3743 ACS patients 14% had acute HF. Acute heart failure patients were older (69.2±12.6 vs 62.3±12.8 years, p<0.001), less likely to have coronary angiography (66% vs 86%, p<0.001) and revascularisation (46% vs 62%, p<0.001). Immediate post-discharge quadruple therapy was higher for those with than without HF (61% vs 55%, p=0.02) but fell to similar levels by one-year (45% vs 53%, p=0.55). At four years follow-up nearly half of those presenting with ACS and HF had died. After adjustment, HF remained a strong predictor of death within 28 days (OR 2.9, 95%CI 1.5 - 5.5) and beyond 28 days (HR 1.8, 95%CI 1.5 - 2.3). CONCLUSION: Acute heart failure complicating ACS is associated with heightened risk of short-term and long-term mortality. One in three ACS patients with HF did not have coronary angiography and less than half received quadruple therapy a year after presentation.

A new approach to assessment of the left ventricle.

Cardiac motion is a continuous process; however most measurements to assess cardiac function are taken at brief moments in the cardiac cycle. Using functional data analysis, repeated measurements of left ventricular volume recorded at each frame of a continuous image measured with cardiac ultrasound (echocardiography) were turned into a function of volume over time. The first derivative of the displacement of volume with respect to time is velocity; the second derivative is acceleration. Plotting volume, velocity, and acceleration against each other in a 3-dimensional plot results in a closed loop. The area within the loop is defined by the kinematics of volume change and so may represent ventricular function. •We have developed an approach to analyzing images of the left ventricle that incorporates information from throughout the cardiac cycle. •Comparing systolic and diastolic areas within a loop defined by volume, velocity, and acceleration of left ventricular volume highlights imbalances in the kinematics of the two phases, potentially indicating early sub-clinical disease.•Substantially more information about left ventricular function may be derived from a non-invasive clinically available tool such as echocardiography.

Is heart rate a risk marker in patients with chronic heart failure and concomitant atrial fibrillation? Results from the MAGGIC meta-analysis.

AIM: To investigate the relationship between heart rate and survival in patients with heart failure (HF) and coexisting atrial fibrillation (AF). METHODS AND RESULTS: Patients with AF included in the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) meta-analysis were the main focus of this analysis (3259 patients from 17 studies). The outcome was all-cause mortality at 3 years. Heart rate was analysed as a categorical (tertiles; T1 ≤77 b.p.m., T2 78-98 b.p.m., T3 ≥98 b.p.m.) and continuous variable. Cox proportional hazard models were used to compare the risk of all-cause death between tertiles of baseline heart rate. Patients in the highest tertile were more often female, less likely to have an ischaemic aetiology or diabetes, had a lower ejection fraction but higher blood pressure and New York Heart Association (NYHA) class. Higher heart rate was associated with higher mortality in patients with sinus rhythm (SR) but not in those in AF. In patients with heart failure and reduced ejection fraction (HF-REF) and AF, death rates per 100 patient years were lowest in the highest heart rate tertile (T1 18.9 vs. T3 15.9) but this difference was not statistically significant (P = 0.10). In patients with heart failure and preserved ejection fraction (HF-PEF), death rates per 100 patient years were highest in the highest heart rate tertile (T1 14.6 vs. T3 16.0, P = 0.014). However, after adjustment for other important prognostic variables, higher heart rate was no longer associated with higher mortality in HF-PEF (or HF-REF). CONCLUSIONS: In this meta-analysis of patients with HF, heart rate does not have the same prognostic significance in patients in AF as it does in those in SR, irrespective of ejection fraction or treatment with beta-blocker.

Higher prevalence of left ventricular hypertrophy in two Maori cohorts: findings from the Hauora Manawa/Community Heart Study.

OBJECTIVES: Cardiovascular disease (CVD) is the leading cause of mortality in New Zealand with a disproportionate burden of disease in the Maori population. The Hauora Manawa Project investigated the prevalence of cardiovascular risk factors and CVD in randomly selected Maori and non-Maori participants. This paper reports the prevalence of structural changes in the heart. METHODS: A total of 252 rural Maori, 243 urban Maori; and 256 urban non-Maori underwent echocardiography to assess cardiac structure and function. Multivariable logistic regression was used to determine variables associated with heart size. RESULTS: Left ventricular (LV) mass measurements were largest in the rural Maori cohort (183.5,sd 61.4), intermediate in the urban Maori cohort (169.7,sd 57.1) and smallest in the non-Maori cohort (152.6,sd 46.7; p<0.001). Similar patterns were observed for other measurements and indexation had no impact. One-third (32.3%) met the gender-based ASE criteria for LV hypertrophy (LVH) with higher prevalence in both Maori cohorts (highest in the rural cohort). There were three significant predictors of LVH: rural Maori (p=0.0001); age (p<0.0001); and gender (p=0.0048). CONCLUSION: Structural and functional heart abnormalities are more prevalent in Maori compared to non-Maori, and especially rural Maori. Early identification should lead to better management, ultimately improving life expectancy and quality of life.

Atrial fibrillation and cycling: six year follow-up of the Taupo bicycle study.

BACKGROUND: Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia, and the incidence of AF is increased markedly among elite athletes. It is not clear how lesser levels of physical activity in the general population influence AF. We asked whether participation in the Taupo Cycle Challenge was associated with increased hospital admissions due to AF, and within the cohort, whether admissions for AF were related to frequency and intensity of cycling. METHODS: Participants in the 2006 Lake Taupo Cycle Challenge, New Zealand's largest mass cycling event, were invited to complete an on-line questionnaire. Those who agreed (n = 2590, response rate = 43.1%) were followed up by record linkage via the National Minimum Health Database from December 1 2006 until June 30 2013, to identify admissions to hospital due to AF. RESULTS: The age and gender standardized admission rate for AF was similar in the Taupo cohort (19.60 per 10,000 per year) and the national population over the same period (2006-2011) (19.45 per 10,000 per year). Within the study cohort (men only), for every additional hour spent cycling per week the risk changed by 0.90 (95% confidence interval 0.79 - 1.01). This result did not change appreciably after adjustment for age and height. CONCLUSIONS: Hospital admission due to AF was not increased above the national rate in this group of non-elite cyclists, and within the group the rate of AF did not increase with amount of cycling. The level of activity undertaken by this cohort of cyclists was, on average, not sufficient to increase the risk of hospitalization for AF.

Self-rated health, health-related behaviours and medical conditions of Maori and non-Maori in advanced age: LiLACS NZ.

AIMS: To establish self-rated health, health-related behaviours and health conditions of Maori and non-Maori in advanced age. METHOD: LiLACS NZ is a longitudinal study. A total of 421 Maori aged 80-90 years and 516 non-Maori aged 85 years living in the Bay of Plenty and Rotorua district were recruited at baseline (2010). Socioeconomic-demographic characteristics and health-related behaviours were established using interviewer administered questionnaire. Self-rated health was obtained from the SF-12. Medical conditions were established from a combination of self-report, review of general practitioner and hospital discharge records, and analyses of fasting blood samples. RESULTS: 61% Maori and 59% non-Maori rated their health from good to excellent. Eleven percent of Maori and 5% of non-Maori smoked; 23% Maori and 47% non-Maori had alcohol on at least 2 occasions per week. Physical activity was higher in Maori than non-Maori (p=0.035) and the relationship was attenuated when adjusted for age. More Maori (49%) than non-Maori (38%) were at high nutrition risk (p=0.005); and more non-Maori (73%) than Maori (59%) were driving (p<0.01). The three most common health conditions were hypertension (83%), eye diseases (58%) and coronary artery disease (44%). The health profile differed by gender and ethnicity. Overall, participants had a median of five health conditions. CONCLUSION: Self-rated health is high in this sample considering the number of comorbidities. There are differences in health behaviours and health conditions between genders and by ethnicity in advanced age. The significance of health conditions in men and women, Maori and non-Maori in advanced age will be examined longitudinally.

Genetic polymorphism rs6922269 in the MTHFD1L gene is associated with survival and baseline active vitamin B12 levels in post-acute coronary syndromes patients.

BACKGROUND AND AIMS: The methylene-tetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L) gene is involved in mitochondrial tetrahydrofolate metabolism. Polymorphisms in MTHFD1L, including rs6922269, have been implicated in risk for coronary artery disease (CAD). We investigated the association between rs6922269 and known metabolic risk factors and survival in two independent cohorts of coronary heart disease patients. METHODS AND RESULTS: DNA and plasma from 1940 patients with acute coronary syndromes were collected a median of 32 days after index hospital admission (Coronary Disease Cohort Study, CDCS). Samples from a validation cohort of 842 patients post-myocardial infarction (PMI) were taken 24-96 hours after hospitalization. DNA samples were genotyped for rs6922269, using a TaqMan assay. Homocysteine and active vitamin B12 were measured by immunoassay in baseline CDCS plasma samples, but not PMI plasma. All cause mortality was documented over follow-up of 4.1 (CDCS) and 8.8 (PMI) years, respectively. rs6922269 genotype frequencies were AA n = 135, 7.0%; GA n = 785, 40.5% and GG n = 1020, 52.5% in the CDCS and similar in the PMI cohort. CDCS patients with AA genotype for rs6922269 had lower levels of co-variate adjusted baseline plasma active vitamin B12 (p = 0.017) and poorer survival than patients with GG or GA genotype (mortality: AA 19.6%, GA 12.0%, GG 11.6%; p = 0.007). In multivariate analysis, rs6922269 genotype predicted survival, independent of established covariate predictors (p = 0.03). However the association between genotype and survival was not validated in the PMI cohort. CONCLUSION: MTHFD1L rs6922269 genotype is associated with active vitamin B12 levels at baseline and may be a marker of prognostic risk in patients with established coronary heart disease.

Predicting survival in heart failure: a risk score based on 39 372 patients from 30 studies.

AIMS: Using a large international database from multiple cohort studies, the aim is to create a generalizable easily used risk score for mortality in patients with heart failure (HF). METHODS AND RESULTS: The MAGGIC meta-analysis includes individual data on 39 372 patients with HF, both reduced and preserved left-ventricular ejection fraction (EF), from 30 cohort studies, six of which were clinical trials. 40.2% of patients died during a median follow-up of 2.5 years. Using multivariable piecewise Poisson regression methods with stepwise variable selection, a final model included 13 highly significant independent predictors of mortality in the following order of predictive strength: age, lower EF, NYHA class, serum creatinine, diabetes, not prescribed beta-blocker, lower systolic BP, lower body mass, time since diagnosis, current smoker, chronic obstructive pulmonary disease, male gender, and not prescribed ACE-inhibitor or angiotensin-receptor blockers. In preserved EF, age was more predictive and systolic BP was less predictive of mortality than in reduced EF. Conversion into an easy-to-use integer risk score identified a very marked gradient in risk, with 3-year mortality rates of 10 and 70% in the bottom quintile and top decile of risk, respectively. CONCLUSION: In patients with HF of both reduced and preserved EF, the influences of readily available predictors of mortality can be quantified in an integer score accessible by an easy-to-use website www.heartfailurerisk.org. The score has the potential for widespread implementation in a clinical setting.

A cohort study comparing cardiovascular risk factors in rural Maori, urban Maori and non-Maori communities in New Zealand.

OBJECTIVES: To understand health disparities in cardiovascular disease (CVD) in the indigenous Maori of New Zealand, diagnosed and undiagnosed CVD risk factors were compared in rural Maori in an area remote from health services with urban Maori and non-Maori in a city well served with health services. DESIGN: Prospective cohort study. SETTING: Hauora Manawa is a cohort study of diagnosed and previously undiagnosed CVD, diabetes and risk factors, based on random selection from electoral rolls of the rural Wairoa District and Christchurch City, New Zealand. PARTICIPANTS: Screening clinics were attended by 252 rural Maori, 243 urban Maori and 256 urban non-Maori, aged 20-64 years. MAIN OUTCOME MEASURES: The study documented personal and family medical history, blood pressure, anthropometrics, fasting lipids, insulin, glucose, HbA1c and urate to identify risk factors in common and those that differ among the three communities. RESULTS: Mean age (SD) was 45.7 (11.5) versus 42.6 (11.2) versus 43.6 (11.5) years in rural Maori, urban Maori and non-Maori, respectively. Age-adjusted rates of diagnosed cardiac disease were not significantly different across the cohorts (7.5% vs 5.8% vs 2.8%, p=0.073). However, rural Maori had significantly higher levels of type-2 diabetes (10.7% vs 3.7% vs 2.4%, p<0.001), diagnosed hypertension (25.0% vs 14.9% vs 10.7%, p<0.001), treated dyslipidaemia (15.7% vs 7.1% vs 2.8%, p<0.001), current smoking (42.8% vs 30.5% vs 15.2%, p<0.001) and age-adjusted body mass index (30.7 (7.3) vs 29.1 (6.4) vs 26.1 (4.5) kg/m(2), p<0.001). Similarly high rates of previously undocumented elevated blood pressure (22.2% vs 23.5% vs 17.6%, p=0.235) and high cholesterol (42.1% vs 54.3% vs 42.2%, p=0.008) were observed across all cohorts. CONCLUSIONS: Supporting integrated rural healthcare to provide screening and management of CVD risk factors would reduce health disparities in this indigenous population.